The effects of a single oral dose of 20 mg of nicorandil were evaluated in 12 untreated patients with mild to moderate essential hypertension. Serial measurements of arterial pressures were obtained by means of an automatic device (Dynamap) up to 120 minutes after drug administration. Forearm hemodynamics were determined with a pulsed Doppler velocimeter, or strain gauge mecanography and plethysmography enabling measurement of the diameter, velocity and flow of the brachial artery as well as the arterial pulse wave velocity and forearm venous tone. In addition, local vascular resistance, compliance and impedance were deduced. Nicorandil administration produced a significant decrease in systolic and diastolic blood pressure, from 18 minutes after dosing which lasted up to the end of the study (i.e., 120 minutes after drug administration) (p less than 0.01). This decrease in blood pressure was not associated with reflex tachycardia. The brachial artery diameter increased significantly (p less than 0.01) with no change in brachial artery blood flow. A decrease in brachial-radial pulse wave velocity and arterial impedance (p less than 0.01) and an increase in arterial compliance were observed. Thus, this study demonstrated an antihypertensive activity of a single oral administration of nicorandil without baroreflex activation. This decrease in blood pressure was associated with a dilation of peripheral large arteries leading to an increase in arterial compliance. Thus, clinical testing to evaluate the antianginal activity of nicorandil, especially in hypertensive patients with coronary heart disease, should be encouraged.